We report the case of a young woman who, over a period of five years was diagnosed and treated for a giant-cell tumour of bone, osteomalacia and fluorosis. A review of the literature revealed a correlation between these three diagnoses, the primary pathology being fluorosis and the remaining symptoms being secondary manifestations. It is important to be aware of this association, especially in regions with endemic skeletal fluorosis.

Endemic fluorosis is a public-health problem in several parts of the world and is characterised by abnormalities of the bones and teeth. Typical descriptions of skeletal radiology in endemic fluorosis have emphasised the presence of osteosclerosis, membranous and ligamentous calcification and exostoses. Other reported radiological features include osteomalacia and osteoporosis.1 We report the case of a young woman with secondary manifestations of fluorosis.

Case report

A 28-year-old woman presented in May 1997 with insidious, progressive pain in the right hip and difficulty in walking. Initially, she had been treated elsewhere and a radiograph (Fig. 1) had revealed an osteolytic lesion in the right proximal femur. (T showed features suggestive of a giant-cell tumour. By the time she presented to us she had sustained a pathological fracture of the neck of the femur (Fig. 2). CT-guided fine-needle aspiration cytology was inconclusive. A clinicoradiological diagnosis of a giant-cell tumour of the femur with a pathological fracture was made and a cemented, modular, bipolar hemiarthroplasty was performed in June 1997. Histopathological examination of the tissue was suggestive of a giant-cell tumour of bone and the clearance biopsy was reported to be normal. The post-operative period was uneventful and she conceived in 1999.

However, four years after surgery, in 2001, she returned with progressive pain in the left hip. She also complained of weakness and pain in her lower ribs and back.

Radiological assessment revealed a pseudo-fracture of the neck of the left femur (Fig. 3) and osteopenia of the vertehrae and ribs. A biochemical profile showed a scrum calcium level of 8.S mg% (normal range 9 to 10..9), a serum phosphate level of 3.8 mg% (normal range 3 to 4..S) and an alkaline phosphatase level of 1000 IU/l (normal range 30 to 115). Renal function tests were normal. A diagnosis of osteomalacia was made and she was treated with calcium and vitamin D supplements. Radiological healing of the pseudofracture and an improvement in her biochemical parameters were seen after treatment, hut with no improvement in her symptoms.

By January 2002, the patient had marked difficulty in standing with severe hone pains. A detailed biochemical and haematological profile was performed, including renal function tests, liver function tests, hormonal assays and urine analysis. The only positive findings were low serum calcium and high serum alkaline phosphatase levels. A fluonde assay of the patient's serum, urine and water source revealed levels which were raised to 86, 63 and 8.4 times above the normal, respectively. The diagnosis of osteomalacia with fluorosis was made.

Discussion

Classical teaching in medicine suggests that all signs and symptoms in a patient should be explained by one diagnosis. In our patient, over a period of five years, three different diagnoses were made, namely giant-cell tumour, osteomalacia and fluorosis. We have attempted to find a correlation between these three diagnoses.

A search of the literature showed that, although the classical appearance of skeletal fluorosis is osteosclerosis, it can also present as osteoporosis or osteomalacia. Wang et al2 found that of 127 patients with clinically-proven endemic fluorosis, osteosclerosis was seen in 54 (43%) and osteopenia in 51 (40%). Of the patients with osteopenia, a pattern of osteoporosis was seen in 28 (22%) and of osteomalacia in 23 (18.1%).

Teotia et al3 reported that of 100 patients with fluorosis, only 55% showed the characteristic radiological findings of osteosclerosis, irregular formation of periosteal bone, ectopic calcification, irregular osteophytosis and exostoses. Unusual radiological manifestations, including osteomalcia, were seen in the remaining 45%.

In a study on 65 subjects on the radiological spectrum of endemic fluorosis, Mithal et al4 reported a predominant osteopenia in 12%. Three patients had features resembling rickets, in the form of metaphyseal fraying and apparent widening of the epiphyscal cartilage. Three also had subperiosteal resorption of the phalanges.

Christie,5 in a study on the spectrum of radiological hone changes in children with fluorosis in Tanzania, reported a combination of osteomalacia, osteoporosis and osteosclerosis. Similar findings were also reported by Krishnamachari.6 He explained the reasons why two different radiological pictures may occur, on the basis of calcium intake, as follows.

In patients with an adequate calcium intake calcium fluroapatite is deposited in bone and leads to an increased bone density. No marked change in ionised serum calcium occurs and the radiological picture is one of osteosclerosis. In those with a poor intake of calcium, calcium fluroapatite formed in the blood leads to a decrease in the level of serum calcium. In addition, fluoride stimulates the parathyroid glands directly or indirectly. Both of these factors can lead to secondary hyperparathyroidism. The radiological picture is one of osteopenia.

In the light of Krishnamachan's work,6 we were reasonably certain that fluorosis was the primary pathology which led to secondary osteomalacia in our patient. The question arose as to whether the giant-cell tumour was an incidental occurrence or a feature of hyperparathyroidism manifesting as a brown tumour and mimicking a giant-cell tumour. A review of the literature showed that various authors have documented the radiological manifestations of secondary hyperparathyroidism caused by fluorosis, such as subperiosteal resorption, generalised osteopenia, loss of the lamina dura and the presence of Looser zones and resorptive cavities.3,6-10 Prolonged stimulation of the parathyroid gland because of secondary hyperparathyroidism which has been caused by fluorosis may cause formation of an adenoma de novo (tertiary hyperparathyroidism).7-11

A review of the initial skeletal survey in our patient revealed a multilocular lytic lesion with a homogenous matrix but without any expansion of the cortex. The lesion had a narrow zone of transition with well-defined margins. The pre-operative CT scan (Fig. 2) showed a pathological fracture and a minimal soft-tissue shadow. The Hounsfield value within the head of femur was 77, which suggested the presence of blood.

The patient's chest radiograph, previously reported as normal, revealed a Looser zone in the left first rib (Fig. 4). Her mandibular radiograph showed a partial loss of the lamina dura. There was also subcortical and intracortical resorption of the phalanges and metacarpals. In view of these radiological features of secondary hyperparathyroidism the radiologist considered that a brown tumour could not be excluded.

With this revised clinicoradiological assessment, we requested a review of the histopathological sections. These were still found to be inconclusive in distinguishing between a giant-cell tumour and a brown tumour.

We believe that the primary pathology in our patient was fluorosis. This led to secondary hyperparathyroidism manifesting as osteomalacia and, ultimately, a resorptive cavity in the head and neck of the femur. Awareness of such an association, especially in a region with endemic fluorosis, is essential.

No benefits in any form have been received or will be received from any commercial party related directly or indirectly to the subject of this article.

References

1. Sivakumar B, Krishnamachari KA. Circulating levels of immunoreactive parathyroid hormone in endemic genu valgum. Harm Metab Res 1976;8:317-19.

2. Wang Y, Yin Y, Gilula LA, Wilson AJ. Endemic fluorosis of the skeleton: radiographic features in 127 patients Am J Roentgenol 1994;162:93-8

3. Teotia SP, Teotia M, Rohatgi VK, Teotia NP. Endemic skeletal fluorosis and metabolic bone disease (a radiological and morphometrical study of bone). J Indian Med Assoc 1974;63:207-11.

4. Mithal A, Trivedi N, Gupta SK, Kumar S, Gupta RK. Radiological spectrum of endemic fluorosis: relationship with calcium intake. Skeletal Radiol 1993;22: 257-61.

5. Christie DP. The spectrum of radiographic bone changes in children in fluorosis. Radiology 1980;136:85-90.

6. Krishnamachari KA. Skeletal fluorosis in humans: a review of recent progress in the understanding of the disease. Prog Food Nutr Sci 1986;10:279-314.

7. Teotia SPS, Teotia M. Secondary hyperparathyroidism in patients with endemic skeletal fluorosis. Br Med J 1973;2:637-40.

8. Teotia SP, Teotia M, Singh RK, Taves DR, Heels S. Endocrine aspects of endemic skeletal fluorosis. J Assoc Physicians India 1978;26:995-1000.

9. Shrivastava RN, Gill DS, Moudgil A, et al. Normal ionized calcium, parathyroid hypersecretion and elevated osteocalcium: a family with fluorosis. Meiabolism 1989; 38:120-4.

10. Gupta SK, Khan TI, Gupta RC, et al. Compensatory hyperparathyroidism following high fluoride ingestion: a clinico-biochemical correlation. Indian Paedatr 2001;38: 139-46.

11. Davies DR, Dent CE, Watson L. Tertiary hyperparathyroidism Br Med J 1968;2: 395-9.

M. Chadha, S. Kumar

From the University College of Medical Sciences and Associated Guru Teg Bahadur Hospital, Delhi, India

* M. Chadha, MS (Orthopaedics), Lecturer

* S. Kumar, MS (Orthopaedics), MCh, Professor and Head

Department of Orthopaedics,

University College of

Medical Sciences and

Associated Guru Teg

Bahadur Hospital, Shahdara,

Delhi-110095, India.

Correspondence should be sent to Dr M. Chadha at C-A/ 16, Tagore Garden, New Delhi-110027, India.

doi: 10.1302/0301-620X.86B4. 14944 $2.00

J Bone Joint Surg [Br] 2004;86-B:594 6.

Received 10 September 2003; Accepted 27 October 2003

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